Neuronal nitric oxide synthase and ischemia-induced neurogenesis

Yunjuan Sun, Kunlin Jin, Jocelyn T. Childs, Lin Xie, Xiao Ou Mao, David A. Greenberg

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Nitric oxide (NO) influences infarct size after focal cerebral ischemia and also regulates neurogenesis in the adult brain. These observations suggest that therapeutic approaches to stroke that target NO signaling may provide neuroprotection and also enhance brain repair through cell replacement. However, ischemic injury and neurogenesis are both affected differently depending on which isoform of NO synthase is the source of NO. In addition, ischemia itself stimulates neurogenesis, and ischemia-induced neurogenesis may be regulated differently than neurogenesis in nonischemic brain. To determine how neuronal NO synthase affects ischemia-induced neurogenesis, transient focal cerebral ischemia was produced in wild-type mice and in knockout mice lacking neuronal NO synthase, and BrdU incorporation and doublecortin immunoreactivity were measured in the principal neuroproliferative regions of the adult brain. Knockout of neuronal NO synthase reduced infarct size and increased both basal and ischemia-induced neurogenesis, suggesting that NO from this source is an inhibitory regulator of neurogenesis in the ischemic brain. 7-Nitroindazole, an NO synthase inhibitor that preferentially affects the neuronal isoform, also increased neurogenesis in rats when administered by the intracerebroventricular route. Selective inhibition of neuronal NO synthase may have the potential to both reduce infarct size and enhance neurogenesis in stroke.

Original languageEnglish
Pages (from-to)485-492
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number4
StatePublished - Apr 2005


  • Bromodeoxyuridine
  • Doublecortin
  • Ischemia
  • Neurogenesis
  • Nitric oxide
  • Nitric oxide synthase


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